Synthesis of pavoninin-1, a shark repellent substance, and its structural analogues toward mechanistic studies on their membrane perturbation.
Pavoninin-1 (1), which was isolated from a defense secretion of the sole Pardachirus spp. as an ichthyotoxic and a shark repellent principle, and its structural analogue 2 were synthesized, where glycosylation using an 2-azidoglycosyl sulfoxide (10) afforded the corresponding beta-glycoside exclusively in high yield. Introduction of the alpha,beta-unsaturated ketone system in the ring A of 1 was achieved by phenylselenenylation of dihydropavoninin-1 (3) and subsequent oxidative elimination without protection of the hydroxyl groups in the sugar portion. The mode of action of these glycosides was evaluated for their perturbation on phosphatidylcholine liposomal membrane, using the fluorescent dye leakage method. The results revealed that membrane affinity does not parallel membrane perturbation but rather compensates it, and the spatial arrangement of hydrophobic and hydrophilic regions within a molecule is likely to reflect on the difference in potency of action among them.
Ohnishi
Y
Y
Department of Chemistry, School of Science, University of Tokyo, Japan.
Tachibana
K
K
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001733:Bites and Stings / Q000517:prevention & control; D002463:Cell Membrane Permeability / Q000187:drug effects; D002783:Cholestenones / Q000138:chemical synthesis* / Q000494:pharmacology; D006031:Glycosylation; D007536:Isomerism; D007695:Killifishes; D008081:Liposomes / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D008567:Membranes, Artificial; D008956:Models, Chemical; D012754:Sharks; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000617:Aminoglycosides; D002783:Cholestenones; D008081:Liposomes; D008563:Membrane Lipids; D008567:Membranes, Artificial; C111198:pavoninin 1